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Zinc-finger protein 545 inhibits cell proliferation as a tumor suppressor through inducing apoptosis and is disrupted by promoter methylation in breast cancer.

Xiao Y, Xiang T, Luo X, Li C, Li Q, Peng W, Li L, Li S, Wang Z, Tang L, Ren G, Tao Q - PLoS ONE (2014)

Bottom Line: In this study, we found that ZNF545 was frequently downregulated in estrogen receptor-positive (ER+), progesterone receptor-positive (PR+) and human epidermal growth factor receptor 2-negative (HER2-) breast tumor tissues compared with paired adjacent non-tumor tissues.We found that ZNF545 was silenced by promoter methylation in MCF7 cell line, and its expression could be restored by demethylation, concomitant with increased unmethylated alleles.Taken together, these results demonstrate that ZNF545 inhibits breast tumor cell proliferation through inducing apoptosis and is disrupted by promoter methylation in breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

ABSTRACT
Krüppel-associated box-containing zinc finger proteins (KRAP-ZFPs) are well recognized as key regulators of transcription, which play a crucial role in the regulation of cell proliferation, differentiation, apoptosis and tumorigenesis. We previously identified a KRAP-ZFP protein ZNF545 acting as a tumor suppressor involved in tumor pathogenesis. However, its expression and biological function in breast cancer remain elusive. In this study, we found that ZNF545 was frequently downregulated in estrogen receptor-positive (ER+), progesterone receptor-positive (PR+) and human epidermal growth factor receptor 2-negative (HER2-) breast tumor tissues compared with paired adjacent non-tumor tissues. We further examined its expression and methylation in breast cancer cell lines by semi-quantitative RT-PCR and methylation-specific PCR. We found that ZNF545 was silenced by promoter methylation in MCF7 cell line, and its expression could be restored by demethylation, concomitant with increased unmethylated alleles. ZNF545 methylation was detected in 29% of breast tumor tissues, but not in normal breast tissues, suggesting tumor-specific methylation of ZNF545 in breast cancer. Ectopic expression of ZNF545 in MCF7 cells inhibited cell proliferation through inducing cell cycle G0/G1 arrest and apoptosis, thus as a tumor suppressor. Moreover, ZNF545 upregulated mRNA and protein levels of c-Jun/AP1, BAX, p53 and Caspase 3. Taken together, these results demonstrate that ZNF545 inhibits breast tumor cell proliferation through inducing apoptosis and is disrupted by promoter methylation in breast cancer.

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ZNF545 is frequently methylated in primary breast tumors.(A) Methylation of ZNF545 by MSP in normal breast tissues. (B) Representative analysis of methylation of the ZNF545 promoter in breast tumor tissues. M, methylated; U, unmethylated.
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pone-0110990-g002: ZNF545 is frequently methylated in primary breast tumors.(A) Methylation of ZNF545 by MSP in normal breast tissues. (B) Representative analysis of methylation of the ZNF545 promoter in breast tumor tissues. M, methylated; U, unmethylated.

Mentions: To investigate ZNF545 promoter methylation in breast tumor tissues, MSP was used to examine 128 primary breast carcinomas tissues and seven normal breast tissues. ZNF545 methylation was detected in 37 out of 128 (29%) breast cancer tissue, but not in normal breast tissues (Fig. 2, Table 4), implying that methylation-mediated ZNF545 inactivation is a common event in breast cancer. These results suggest that ZNF545 is under tumor-specific methylation in breast cancer.


Zinc-finger protein 545 inhibits cell proliferation as a tumor suppressor through inducing apoptosis and is disrupted by promoter methylation in breast cancer.

Xiao Y, Xiang T, Luo X, Li C, Li Q, Peng W, Li L, Li S, Wang Z, Tang L, Ren G, Tao Q - PLoS ONE (2014)

ZNF545 is frequently methylated in primary breast tumors.(A) Methylation of ZNF545 by MSP in normal breast tissues. (B) Representative analysis of methylation of the ZNF545 promoter in breast tumor tissues. M, methylated; U, unmethylated.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215924&req=5

pone-0110990-g002: ZNF545 is frequently methylated in primary breast tumors.(A) Methylation of ZNF545 by MSP in normal breast tissues. (B) Representative analysis of methylation of the ZNF545 promoter in breast tumor tissues. M, methylated; U, unmethylated.
Mentions: To investigate ZNF545 promoter methylation in breast tumor tissues, MSP was used to examine 128 primary breast carcinomas tissues and seven normal breast tissues. ZNF545 methylation was detected in 37 out of 128 (29%) breast cancer tissue, but not in normal breast tissues (Fig. 2, Table 4), implying that methylation-mediated ZNF545 inactivation is a common event in breast cancer. These results suggest that ZNF545 is under tumor-specific methylation in breast cancer.

Bottom Line: In this study, we found that ZNF545 was frequently downregulated in estrogen receptor-positive (ER+), progesterone receptor-positive (PR+) and human epidermal growth factor receptor 2-negative (HER2-) breast tumor tissues compared with paired adjacent non-tumor tissues.We found that ZNF545 was silenced by promoter methylation in MCF7 cell line, and its expression could be restored by demethylation, concomitant with increased unmethylated alleles.Taken together, these results demonstrate that ZNF545 inhibits breast tumor cell proliferation through inducing apoptosis and is disrupted by promoter methylation in breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

ABSTRACT
Krüppel-associated box-containing zinc finger proteins (KRAP-ZFPs) are well recognized as key regulators of transcription, which play a crucial role in the regulation of cell proliferation, differentiation, apoptosis and tumorigenesis. We previously identified a KRAP-ZFP protein ZNF545 acting as a tumor suppressor involved in tumor pathogenesis. However, its expression and biological function in breast cancer remain elusive. In this study, we found that ZNF545 was frequently downregulated in estrogen receptor-positive (ER+), progesterone receptor-positive (PR+) and human epidermal growth factor receptor 2-negative (HER2-) breast tumor tissues compared with paired adjacent non-tumor tissues. We further examined its expression and methylation in breast cancer cell lines by semi-quantitative RT-PCR and methylation-specific PCR. We found that ZNF545 was silenced by promoter methylation in MCF7 cell line, and its expression could be restored by demethylation, concomitant with increased unmethylated alleles. ZNF545 methylation was detected in 29% of breast tumor tissues, but not in normal breast tissues, suggesting tumor-specific methylation of ZNF545 in breast cancer. Ectopic expression of ZNF545 in MCF7 cells inhibited cell proliferation through inducing cell cycle G0/G1 arrest and apoptosis, thus as a tumor suppressor. Moreover, ZNF545 upregulated mRNA and protein levels of c-Jun/AP1, BAX, p53 and Caspase 3. Taken together, these results demonstrate that ZNF545 inhibits breast tumor cell proliferation through inducing apoptosis and is disrupted by promoter methylation in breast cancer.

Show MeSH
Related in: MedlinePlus